Retrovirus-elicited interleukin-12 and tumour necrosis factor-alpha as inducers of interferon-gamma-mediated pathology in mouse AIDS.

Journal Article (Journal Article)

Spleen cells from mice resistant or sensitive to mouse acquired immune deficiency syndrome (MAIDS) were examined for cytokine mRNA. In MAIDS-resistant BALB/c mice, cytokine transcripts peaked at 1 week after infection with Type 1 cytokines [interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-12], dominating over Type 2 cytokines (IL-4, IL-10). Expression of cytokines other than IL-2 later declined to levels seen in uninfected mice. In MAIDS-sensitive B6 mice, transcripts for all cytokines were increased at 1 week and, except for IL-2, increased progressively. Spontaneous production of IFN-gamma protein was associated with enhanced mRNA expression at 1 week after infection of either strain, but none was detectable in association with even higher levels of transcripts at later times after infection of B6 mice. Spleen cells from longer-term-infected B6 mice, however, produced substantial amounts of IFN-gamma following treatment with lipopolysaccharide (LPS) or IL-12. Inclusion of anti-IL-12 or anti-TNF-alpha antibodies blocked induction of IFN-gamma by LPS. Induction of IFN-gamma by IL-12 was potentiated by TNF-alpha following stimulation of intact spleen cells and purified CD4+ or CD8+ T cells, as well as negatively selected CD4-8- cells from infected B6 mice. Further studies showed that IFN-gamma knockout mice on a B6 background developed MAIDS with a prolonged time-course, whereas BALB/c knockout mice were unchanged in their resistance to MAIDS. These studies suggest that continuing low-level expression of IFN-gamma, stimulated by IL-12 and TNF-alpha, contributes to the susceptibility of B6 mice to MAIDS but is not required for the resistance of BALB/c mice to disease.

Full Text

Duke Authors

Cited Authors

  • Giese, NA; Gazzinelli, RT; Actor, JK; Morawetz, RA; Sarzotti, M; Morse, HC

Published Date

  • March 1996

Published In

Volume / Issue

  • 87 / 3

Start / End Page

  • 467 - 474

PubMed ID

  • 8778035

Pubmed Central ID

  • PMC1384118

International Standard Serial Number (ISSN)

  • 0019-2805

Digital Object Identifier (DOI)

  • 10.1046/j.1365-2567.1996.492569.x


  • eng

Conference Location

  • England